Association of myostatin deficiency with collagen related disease-umbilical hernia and tippy toe standing in pigs

• Published in: Transgenic research Vol. 30; no. 5; pp. 663 - 674
• Main Authors: Paek, Hyo-Jin, Luo, Zhao-Bo, Choe, Hak-Myong, Quan, Biao-Hu, Gao, Kai, Han, Sheng-Zhong, Li, Zhou-Yan, Kang, Jin-Dan, Yin, Xi-Jun
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-10-2021; Springer Nature B.V
• Subjects: Activin; Animal Genetics and Genomics; Animals; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Body weight; Collagen; Collagen (type I); Collagen - genetics; Cyclin-dependent kinase; Cyclin-dependent kinase inhibitor p21; Cyclin-dependent kinases; Enzyme inhibitors; Fibroblasts; Gene expression; Genetic Engineering; Hernia; Hernia, Umbilical - genetics; Hernias; Kinases; Life Sciences; Male; Molecular Medicine; Muscle, Skeletal; Myostatin; Myostatin - genetics; Nuclear transfer; Nuclear Transfer Techniques; Original Paper; Phosphorylation; Plant Genetics and Genomics; Smad2 protein; Somatic cell nuclear transfer; Swine; Therapeutic targets; Toes; Transgenics; Myostatin; Scleraxis; Umbilical hernia; Type 1 collagen; Tendon
• ISSN: 0962-8819; 1573-9368
• DOI: 10.1007/s11248-021-00275-6

Herein, we investigate the high incidence of umbilical hernia and tippy-toe standing and their underlying changes in gene expression and proliferation in myostatin knockout (
MSTN
−/−
) pigs. Thirty-six male
MSTN
−/−
pigs were generated by somatic cell nuclear transfer (SCNT). These pigs presented a considerably high incidence of tippy-toe standing and umbilical hernia (69.4% and 61.1%, respectively). The tendon to body weight ratio was significantly lower than wild-type pigs (0.202 ± 0.017 vs 0.250 ± 0.004, respectively). The crimp length of the
MSTN
−/−
tendon was significantly longer than that of wild-type pigs. The expression of
MSTN
and the activin type IIB (
ACVR2B
) was detected in the tendon and linea alba of
MSTN
−/−
pigs. MSTN treatment significantly increased the phosphorylation of Smad2/3 in both tendon and linea alba fibroblasts. Type I collagen (
Col1A
) and Scleraxis (
Scx
) expression levels in the tendon and linea alba of
MSTN
−/−
pigs were significantly lower than those in wild-type in vivo, whereas and cyclin-dependent kinase inhibitor 1 (
p21
) expression levels were higher. Treatment of tendon and linea alba fibroblasts with recombinant MSTN increased
Col1A
and
Scx
and decreased
p21
expression in vivo. Moreover, there was a significant increase in fibroblast proliferation after treatment. The results indicated that MSTN regulates collagen expression and proliferation in tendon and linea alba fibroblasts; thus,
MSTN
deficiency causes collagen-related pathological features in
MSTN
−/−
pigs. Hence, MSTN could be used as a therapeutic target for treating UH and tendon abnormalities.